Perioperative Management of Aneurysmal Subarachnoid Hemorrhage: A Narrative Review
Highlights
- Up to 15% patients with aneurysmal subarachnoid hemorrhage may die before reaching the hospital (View Highlight)
- Most spontaneous (nontraumatic) subarachnoid hemorrhages are caused by ruptured saccular aneurysms (View Highlight)
- The patients with aneurysmal subarachnoid hemorrhage are significantly younger than those with other types of stroke, and women have 1.24 times greater risk of aneurysmal subarachnoid hemorrhage than men (View Highlight)
- Despite substantial advancements in the care of patients with aneurysmal subarachnoid hemorrhage, the mortality rates are 32% to 67%, and a third of the survivors remain dependent (View Highlight)
- The subarachnoid hemorrhage may lead to loss of consciousness owing to global cerebral ischemia resulting from increased intracranial pressure (ICP), decreased cerebral perfusion pressure (CPP), and reduced cerebral blood flow (View Highlight)
- Acute increase in cerebrovascular resistance results in highly pulsatile flow pattern, with much reduced diastolic blood flow velocity on transcranial Doppler ultrasonography and oscillating flow pattern (anterograde flow in systole and retrograde flow in diastole) indicating zero net flow if the ICP surpasses systemic blood pressure (View Highlight)
- A compensatory sympathetic response involving systemic hypertension ensues within minutes.25 Vasoactive mediators such as thromboxane and serotonin are released within minutes to hours of subarachnoid hemorrhage, leading to microcirculatory constriction.29 Blood–brain barrier disruption, cerebral edema, and a thromboinflammatory cascade ensue soon thereafter (View Highlight)
- Within hours or days, transient ischemic events increase the cerebrospinal fluid (CSF) level of endothelin-1.29 These mechanisms combined with the phosphorylation of vascular endothelial growth factor and mitogen-activation protein kinase in the intracranial arteries cause the early brain injury (View Highlight)
- The delayed cerebral ischemia may be the manifestation of interplay of pathophysiologic phenomena, including loss of cerebrovascular autoregulation, cerebral vasospasm, microvascular thrombosis, neuroinflammation, and cortical spreading depolarization (View Highlight)
- The elimination of blood clot within the subarachnoid space starts typically 3 days after subarachnoid hemorrhage, releasing oxyhemoglobin from the erythrocytes, leading to decreased levels of nitric oxide and contributing to delayed cerebral vasospasm.29,30 Blood in cerebral cisterns can occlude arachnoid granulations, preventing reabsorption of CSF and thereby leading to delayed hydrocephalus a few weeks after the aneurysmal subarachnoid hemorrhage. (View Highlight)
(View Highlight)- Xanthochromia resulting from breakdown of hemoglobin in the CSF is typically detectable 12 h after the clinical presentation (View Highlight)
- Broad goals of early management include (1) maintenance of oxygenation and ventilation; (2) rapid restoration of cerebral perfusion; (3) prevention of rebleeding; (4) seizure prophylaxis; (5) initiation of nimodipine, and; (6) planning timely definitive care (View Highlight)
- Tracheal intubation and mechanical intubation is required if (1) the patient remains comatose and is unable to protect his/her airway; (2) there is hypoxia or hypoventilation; (3) patient is hemodynamically unstable, or; (4) there is need for heavy sedation and/or pharmacologic paralysis to keep the patient safe (e.g., owing to excessive agitation during imaging or external ventricular drain placement) (View Highlight)
- The absence of neurologic improvement after external ventricular drain placement and normalization of ICP may indicate other treatable factors such as seizures (View Highlight)
- Excessive or rapid loss of CSF during external ventricular drain placement can acutely increase the transmural pressure leading to rebleeding, and must be avoided (View Highlight)
- Aneurysm rebleeding has high mortality and must be avoided. The risk of rebleeding during the first 24 h is 4% to 13.6%.59–61 Factors associated with rebleeding include initial loss of consciousness, delayed treatment, worse neurologic status on admission, history of sentinel headaches, larger aneurysm size, and systolic blood pressure greater than 160 mmHg (View Highlight)
- the systolic blood pressure should be maintained at less than 160 mmHg (View Highlight)
- Some suitable pharmacologic choices include nicardipine, esmolol, and clevidipine, although there are no data comparing their relative effectiveness (View Highlight)
- While treating acute increases in blood pressure, it is critical to avoid hypotension because the benefit of reduced rebleeding with antihypertensive therapy may be potentially offset by increased risk of cerebral infarction (View Highlight)
- Brain tissue hypoxia may occur in patients with poor-grade subarachnoid hemorrhage at CPP less than 70 mmHg (View Highlight)
- Warfarin should be reversed with prothrombin complex concentrate (PCC) and vitamin K. Fresh frozen plasma can be used in the absence of PCC (View Highlight)
- Idarucizumab, a monoclonal antibody fragment, is the specific reversal agent for dabigatran.66 When Idarucizumab is not available, four-factor PCC or activated PCC may be used (View Highlight)
- Short-term (less than 72 h) use of antifibrinolytic aminocaproic acid or tranexamic acid is allowable to reduce the risk of rebleeding if a delay in the definitive treatment of the aneurysm is unavoidable (View Highlight)
- Although seizures are likely to worsen the neurologic injury after aneurysmal subarachnoid hemorrhage and may precipitate rebleeding, there is lack of consensus around the use of prophylactic anticonvulsant therapy after aneurysmal subarachnoid hemorrhage (View Highlight)
- Initiation of seizure prophylaxis is reasonable in the immediate posthemorrhage period in patients with poor neurologic grade, unsecured aneurysm, and associated intracerebral hemorrhage (View Highlight)
- Nimodipine has been convincingly shown to improve outcomes of aneurysmal subarachnoid hemorrhage despite any favorable effect on angiographic or symptomatic vasospasm.70–75 Possible mechanisms responsible for the effectiveness of nimodipine may include dilation of smaller arteries not visible on angiograms, reduction of calcium-dependent excitotoxicity, and reduced platelet aggregation (View Highlight)
- Administration of 60 mg nimodipine orally or by nasogastric tube every 4 h, starting within 48 h of aneurysmal subarachnoid hemorrhage and continued for 21 days, is considered a standard of care.63 The dose may have to be reduced or it may have to be discontinued because of the hypotension, especially in patients with higher grades of subarachnoid hemorrhage (View Highlight)
- Because the incidence of delayed cerebral ischemia is increased when nimodipine is interrupted,77,78 it is recommended to first use vasopressors to treat hypotension. If this is ineffective, dose may be reduced to half and, in cases of refractory hypotension, nimodipine may have to be stopped. (View Highlight)
- surgical clipping is preferred in patients with large intraparenchymal hematomas, aneurysm of the middle cerebral artery, and in those not likely to be compliant with long-term follow-up (View Highlight)
- Endovascular treatment is usually preferred in the geriatric patients, particularly those presenting with high-grade aneurysmal subarachnoid hemorrhage from the rupture of basilar apex aneurysm (View Highlight)
- Patients with worse neurologic status and higher-grade aneurysmal subarachnoid hemorrhage are more likely to have raised intracranial hypertension, intraoperative brain swelling, impaired cerebral autoregulation, and impaired cerebrovascular reactivity to carbon dioxide (View Highlight)
- Elevated plasma norepinephrine may be primarily contributory to aneurysmal subarachnoid hemorrhage–induced pulmonary edema, although both epinephrine and norepinephrine appear to be involved.100 Direct irritation of the brainstem, causing a direct neurogenic stimulation of the lungs, has also been suggested as a possible mechanism of neurogenic pulmonary edema. (View Highlight)
- Possible pathophysiological mechanisms for neurogenic stunned myocardium include hypothalamic and myocardial perivascular/microvascular lesions associated with a catecholamine surge (View Highlight)
- Electrocardiographic changes, especially in hemodynamically stable patients, should not delay urgent surgery for further investigations. Interestingly, QTc prolongation, bradycardia, conduction abnormality, and echocardiographic changes recover postoperatively (View Highlight)
- Urgent aneurysm clipping can proceed safely even in patients with Takotsubo cardiomyopathy although more vigilant perioperative monitoring is needed (View Highlight)
- Cerebral salt wasting is typically responsible for hyponatremia owing to increased secretion of brain natriuretic peptide with subsequent suppression of aldosterone synthesis (View Highlight)
- in aneurysmal subarachnoid hemorrhage with anterior circulation aneurysms, the syndrome of inappropriate antidiuretic hormone secretion (SIADH) may be more common (View Highlight)
- For complex aneurysms requiring trapping coupled with high-flow arterial or venous grafts and reconstruction surgery, anesthesiologists should be prepared for prolonged temporary occlusion times and potential for major blood loss requiring transfusion. (View Highlight)
- Succinylcholine may be used safely without concerns for increased ICP after ensuring adequate anesthetic depth (View Highlight)
- Monitoring of the electroencephalogram (EEG) may be needed if a decision is made to use burst suppression during temporary clipping (View Highlight)
- Temporary clipping may cause cerebral ischemia and symptomatic strokes in up to 10% to 12% patients (View Highlight)
- Prolongation of central conduction time on SSEPs to greater than 10 ms or a reduction in the amplitude of cortical N20 component of SSEP by greater than 50% is considered clinically significant and indicative of ongoing cerebral ischemia (View Highlight)
- SSEP monitoring has significant utility in clipping anterior circulation aneurysms because the amplitude of SSEPs reflects perfusion to the middle and anterior cerebral artery territories (View Highlight)
- motor-evoked potentials can quickly detect subcortical ischemia during surgery, especially pure motor deficits caused by perforating arteries or large branches.139,140 For ischemia of short duration, the motor-evoked potential signals typically recover with reposition of the clip (View Highlight)
- motor-evoked potential amplitude is decreased, and latency is increased during deep anesthesia. In fact, during EEG burst suppression, motor-evoked potentials may not be reliably recorded, limiting their diagnostic accuracy (View Highlight)
- The external ventricular drain should be used to monitor ICP and CPP. It should be referenced at the level of external auditory meatus58 and typically left open to drain CSF if the ICP exceeds 20 mmHg (View Highlight)
- The ideal anesthetic agent for aneurysmal subarachnoid hemorrhage should (1) reduce the cerebral metabolic rate; (2) avoid intracranial hypertension; (3) maintain adequate cerebral blood flow; (4) maintain hemodynamic stability; (5) provide neuroprotection; (6) not interfere with neurophysiological monitoring, and; (7) be easily titrated to the required anesthetic depth allowing rapid emergence (View Highlight)
- Propofol maintains the coupling between cerebral metabolic rate and cerebral blood flow while inhaled anesthetics have a dose-dependent effect on the cerebral blood flow, with higher doses increasing cerebral blood flow despite reducing cerebral metabolic rate (View Highlight)
- Inhaled anesthetics typically decrease cerebral blood flow when used in less than 1.0 MAC (minimum alveolar concentration) doses but tend to cause cerebral vasodilation at higher concentrations leading to uncoupling between cerebral blood flow and metabolism (View Highlight)
- High-dose desflurane has been shown to increase brain tissue oxygenation in patients with aneurysmal subarachnoid hemorrhage and to improve brain tissue acidosis in patients with high-grade aneurysmal subarachnoid hemorrhage during temporary clipping.28 Conversely, in patients with increased intracranial elastance (reduced compliance), this “luxury perfusion” can worsen brain swelling (View Highlight)
- Isoflurane has been shown to cause more cerebral vasodilation than sevoflurane at similar anesthetic concentration.145 However, the cerebral vasodilatory effect of inhalational agents can be minimized by hyperventilation (View Highlight)
- hypocapnia in patients under propofol anesthesia may lead to excessive cerebral vasoconstriction and cerebral ischemia (View Highlight)
- given the physiologic rationale and the potential to offset brain swelling by avoidance of cerebral vasodilatation, it may be advantageous to prefer propofol anesthesia in patients with high-grade aneurysmal subarachnoid hemorrhage with raised ICP. (View Highlight)
- Although inhalational agents cause dose-dependent increases in latency and decreases in amplitude of SSEPs, less than 1.0 MAC concentration is compatible with monitoring of cortical SSEPs although propofol anesthesia does not affect SSEPs.149 Nevertheless, if motor-evoked potential monitoring is contemplated, propofol anesthesia may be preferred especially in patients with preexisting neurologic deficits, although less than 0.5 MAC desflurane is also compatible with motor-evoked potentials (View Highlight)
- Nitrous oxide is generally avoided because of its cerebral vasodilatory effects, increasing cerebral blood flow and cerebral blood volume. It should be avoided if there is evidence of intracranial air (e.g., resulting from external ventricular drain placement153 (View Highlight)
- Dexmedetomidine, an α2-adrenoceptor agonist, is a useful adjunct for craniotomy.156 Potential advantages include reduction of anesthetic and opioid requirements, attenuation of neuroendocrine and hemodynamic responses, reduced use of antihypertensive agents, and faster emergence.157 However, it may adversely affect evoked potentials (View Highlight)
- The susceptibility of transcranial motor-evoked potentials to dexmedetomidine is dependent of targeted blood levels of the drug. As an adjunct to propofol, dexmedetomidine at target plasma concentrations of 0.6–0.8 ng/ml can significantly attenuate the amplitude of transcranial motor-evoked potentials (View Highlight)
- Sedation with ketamine in patients with aneurysmal subarachnoid hemorrhage has been deemed safe. It can also reduce ICP, vasopressor use, cerebral infarction, and spreading depolarizations (View Highlight)
- Adding ketamine to a background anesthetic likely blunts its property of central nervous “excitation” and increases the “depth of anesthesia” evident by a decrease in total EEG power.164 Given its analgesic and neuroprotective potential, it may be used as an adjunct during surgery for aneurysmal subarachnoid hemorrhage, although bolus doses my impair transcranial motor-evoked potentials and should be avoided (View Highlight)
- the anesthesiologists should (1) avoid hypertension before the aneurysm is secured; (2) induce brief periods of hypertension during temporary clipping of a feeding vessel; and (3) normalize blood pressure goals after the aneurysm is secured (View Highlight)
- The current recommendation is to maintain systolic blood pressure less than 160 mmHg.63 CPP less than 70 mmHg may increase the risk of cerebral ischemia in patients with higher-grade aneurysmal subarachnoid hemorrhage65,166 and, hence, relative hypotension is also undesirable (View Highlight)
- To ensure perfusion of the “at-risk” brain during temporary clipping through collateral channels, it is recommended that the blood pressure be raised 10% to 20% above the patient’s baseline. Once the aneurysm is successfully secured, blood pressure can be normalized (View Highlight)
- To facilitate surgical exposure of the aneurysm and to avoid the risk of brain injury associated with retraction pressure applied to the brain, it is critical to provide “brain relaxation (View Highlight)
- The timing of hyperventilation is important. Aggressive hyperventilation should not be instituted before opening of the dura because the resulting increase in the transmural pressure (fig. 1) can precipitate rebleeding (View Highlight)
- Hypertonic saline augments cerebral blood flow in patients with poor-grade aneurysmal subarachnoid hemorrhage and significantly improves cerebral oxygenation (View Highlight)
- drainage of CSF is an effective method for rapid ICP reduction but should be used cautiously. Excessive drainage of CSF with the closed dura may lead to sudden increase in the transmural pressure with possible risk of rebleeding (View Highlight)
- A temporary clip may be placed on the parent vessel to reduce blood flow through the aneurysm, facilitating the dissection and the accurate placement of a permanent clip around the neck of the aneurysm while avoiding aneurysm rupture. However, it exposes the downstream brain tissue to potential ischemia. A temporary clip may be applied for a duration of up to 10 min without ischemia of the middle cerebral artery territory (View Highlight)
- Potential strategies to prevent ischemic damage during temporary clipping include (1) avoiding prolonged temporary clipping (typically greater than 10 min); (2) intraoperative neurophysiological monitoring to alert a signal change due to ischemia and to guide reperfusion; (3) reducing cerebral metabolic demand during temporary clipping (e.g., burst suppression, hypothermia), and; (4) induced hypertension to recruit collateral flow. (View Highlight)
- The notion that reduction in cerebral metabolic rate by pharmacologically induced burst suppression on the EEG is neuroprotective against cerebral ischemia during temporary clipping is not fully substantiated. However, if temporary occlusion is required for more than 10 min, intravenous administration of pentobarbital, propofol or etomidate titrated to achieve EEG burst suppression has been shown to reduce new infarction on postoperative imaging (View Highlight)
- Patients with temporary clip duration of greater than 20 min had less favorable outcome despite receiving thiopental or etomidate for neuroprotection (View Highlight)
- Although routine use of supplemental medications to induce burst suppression is not required, it may be advantageous in patients with high-grade aneurysmal subarachnoid hemorrhage with inadequate collaterals and complex aneurysm when prolonged temporary clipping is anticipated, provided hypotension from the bolus drug can be avoided (View Highlight)
- Although there are no definitive data, it is reasonable to induce hypertension during anticipated prolonged temporary vessel occlusion.63 Usually, blood pressure is increased to 10% to 20% above preinduction baseline value during temporary clipping to recruit collateral blood flow to the territory at risk of ischemia (View Highlight)
- intraoperative hypothermia cannot be recommended for neuroprotection in patients with good grade aneurysmal subarachnoid hemorrhage but may be an option in selected cases.63 Importantly, hyperthermia is detrimental and should be avoided (View Highlight)
- Intraoperative hyperglycemia during aneurysm clipping is associated with increased risk of cognitive changes at glucose concentrations greater than 129 mg/dL and neurologic deficits at glucose concentrations greater than 152 mg/dL.187 Intraoperative glucose greater than 180 mg/dL has been shown to be independently associated with postoperative new-onset composite infections in a mixed neurosurgical population undergoing craniotomy for a variety of indications (View Highlight)
- Adenosine is a dromotropic and chronotropic agent with rapid onset and short duration of action that causes bradycardia progressing into a brief asystole. The duration of adenosine-induced asystole is dose dependent and is variable.191,192 A dose of 0.29–0.44 mg/kg leads to approximately 57 (range, 26–105) seconds of moderate hypotension (View Highlight)
- Adenosine is best avoided in patients with coronary artery disease or abnormalities of the cardiac conduction system as well as in patients with reactive airways disease (View Highlight)
- Compared with adenosine, rapid ventricular pacing allows better control of the start time, the length of pacing, and the induced flow/pressure reduction under controlled conditions.199,200 Yet, given the global reduction of cerebral blood flow, the duration of rapid ventricular pacing should be minimized to avoid cerebral ischemia (View Highlight)
- Cerebral vasospasm is a devastating complication of aneurysmal subarachnoid hemorrhage. It is the result of macro- and microvascular spasms typically between 3 and 14 days posthemorrhage, although it can occasionally persist up to 21 days. (View Highlight)
- Angiographic vasospasm may be seen in up to 70% to 90% of patients.203,204 However, symptomatic vasospasm affects only about a third of the patients (View Highlight)
- The most concerning complication of vasospasm is delayed cerebral ischemia leading to cerebral infarction, although delayed cerebral ischemia can also occur in the absence of vasospasm (View Highlight)
- Despite any demonstrated benefit on improving angiographic vasospasm, oral nimodipine is the only agent currently known to reduce delayed cerebral ischemia (View Highlight)